pH-değişimine duyarlı hidrojellerin/nanopartikul hazırlanması ve ilaç taşınımı için kullanılabilirliğinin araştırılması

Oral administration of the drugs is considered as one of the most convenient and comfortable routes. However, an effective oral delivery of insulin still remains a challenging and elusive goal, due to bioavailability problem. The aim of our work is to develop a pH sensitive system for the oral delivery of insulin based on a unique polymeric combination of a poly (ε-caprolactone) (PCL) core coated with a layers of chitosan (CS) and alginate (ALG). The particles were prepared based on the double emulsion (water/oil/water) solvent evaporation method. The effect of blending hydrophilic Pluronic127 (F127) into the hydrophobic PCL matrix to improve its water permeability properties were investigated. The results showed that blending F127 into the PCL matrix improved it is water permeability by creating porosity in the nanoparticles. ALG have been chosen to provide the needed pH-sensitivity to the system. However, to coat the PCL surface with this anionic ALG layer a cationic CS layer have been added. The effect of each of the CS and ALG layers on the nanoparticle's physiochemical properties (size, encapsulation efficiency and surface charge) were investigated. The results showed that CS and ALG layer addition increased the stability of the nanoprticles. The in-vitro release studies using two different pH environment (1.2 and 7.4) to simulate the physiological conditions in gastriointestinal tract (GIT) showed that, the particles have pH-responsive release patterns. The kinetics studies of the particles release mechanism showed that, the insulin release from all the particles formulations described by the Korsmeyer- Peppas kinetic model and obeying the Fickian diffusion mechanism.